Chapter 85: Pneumococcal Infections

• Streptococcus pneumoniae (the pneumococcus) is a gram-positive coccus that grows in chains, causes α-hemolysis on blood agar, is bile soluble, and is sensitive to optochin.

• Nearly every clinical isolate has a polysaccharide capsule that protects the bacteria from phagocytosis in the absence of type-specific antibody; 93 distinct capsules have been identified.

• In industrialized countries, children serve as the major vectors of pneumococcal transmission: 20–50% of children <5 years old have asymptomatic nasopharyngeal colonization with S. pneumoniae (compared with 5–15% of young and middle-aged adults). Colonization rates for all age groups are even higher in low-income countries.

• Rates of pneumococcal disease vary by season (higher in winter), gender (higher for males), and underlying medical condition (e.g., higher with splenic dysfunction; chronic respiratory, heart, liver, and kidney disease; immunosuppression).

• The introduction and widespread use (in industrialized countries) of pneumococcal conjugate vaccines have led to dramatic changes in the epidemiology of invasive pneumococcal disease; rates have fallen by >75% among infants and children in the United States.

• Nasopharyngeal colonization can persist for many months, resulting in the development of type-specific serum IgG that ultimately leads to pneumococcal clearance from the nasopharynx. Accordingly, pneumococcal disease is usually associated with recent acquisition of a new colonizing serotype.

• Once the nasopharynx has been colonized, the bacteria spread either via the bloodstream to distant sites (e.g., brain, joint, bones) or locally to contiguous areas (e.g., middle ear, lungs).

• Local cytokine production, particularly after intercurrent viral infections, facilitates pneumococcal adherence. Bacterial factors such as peptidoglycan and teichoic acid induce inflammation, result in characteristic pathology, and permit bacterial invasion.

The clinical manifestations of pneumococcal disease depend on the site of infection and the duration of illness.

Pneumonia

Pneumococcal pneumonia—the most common serious pneumococcal syndrome—is difficult to distinguish from pneumonia of other etiologies on the basis of clinical findings.

• Pts often present with fever, abrupt-onset cough and dyspnea, and sputum production.

  • – Pts may also have pleuritic chest pain, shaking chills, or myalgias.

  • – Among the elderly, presenting signs and symptoms may be less specific, with confusion and malaise but without fever or cough.

• On physical examination, adults may have tachypnea (>30 breaths/min) and tachycardia, crackles on chest auscultation, and dullness to percussion of the chest in areas of consolidation.

  • – In some cases, hypotension, bronchial breathing, a pleural rub, or cyanosis may be present.

  • – Upper abdominal pain may be present if the diaphragmatic pleura is involved.

• Pneumococcal pneumonia is generally diagnosed by Gram’s staining and culture of sputum.

  • – While culture results are awaited, chest x-rays—which classically demonstrate lobar or segmental consolidation—may provide some adjunctive evidence, although they may be normal early in the course of illness or with dehydration.

  • – Blood cultures are positive for pneumococci in <30% of cases.

  • – Leukocytosis (>15,000/μL) is common; leukopenia is documented in <10% of cases and is associated with a fatal outcome.

  • – A positive pneumococcal urinary antigen test has a high predictive value among adults, in whom the prevalence of nasopharyngeal colonization is low.

• Empyema occurs in <5% of cases and should be considered when a pleural effusion is accompanied by fever and leukocytosis after 4–5 days of appropriate antibiotic therapy. Pleural fluid with frank pus, bacteria, or a pH of ≤7.1 indicates empyema and requires aggressive drainage.

Meningitis

S. pneumoniae is among the most common causes of meningitis in both adults and children. Pneumococcal meningitis can present as a primary syndrome or as a complication of other pneumococcal conditions (e.g., otitis media, infected skull fracture, bacteremia). Pneumococcal meningitis is clinically indistinguishable from pyogenic meningitis of other etiologies.

• Pts have fever, headache, neck stiffness, photophobia, and occasionally seizures and confusion.

• On examination, pts have a toxic appearance, altered consciousness, bradycardia, and hypertension (indicative of increased intracranial pressure). Kernig’s or Brudzinski’s sign or cranial nerve palsies (particularly of the third and sixth cranial nerves) are noted in a small fraction of adult pts.

• Diagnosis of pneumococcal meningitis relies on examination of CSF, which reveals an elevated protein level, elevated WBC count, and reduced glucose concentration. The etiologic agent can be specifically identified by culture, antigen testing, or PCR. A blood culture positive for S. pneumoniae in conjunction with clinical manifestations of meningitis is also considered confirmatory.

Other Invasive Syndromes

S. pneumoniae can affect virtually any body site and cause invasive syndromes, including bacteremia, osteomyelitis, septic arthritis, endocarditis, pericarditis, and peritonitis. The essential diagnostic approach is collection of fluid from the site of infection by sterile technique and examination by Gram’s staining, culture, and—when relevant—capsular antigen assay or PCR. Hemolytic-uremic syndrome can complicate invasive pneumococcal disease.

Noninvasive Syndromes

Sinusitis and otitis media are the two most common noninvasive syndromes caused by S. pneumoniae; the latter is the most common pneumococcal syndrome and most often affects young children. See Chap. 58 for more detail.

• Outpatient treatment: Amoxicillin (1 g PO q8h) is effective for virtually all cases of pneumococcal pneumonia. Fluoroquinolones (e.g., levofloxacin, 500–750 mg/d; or moxifloxacin, 400 mg/d) are also highly likely to be effective in the United States, although they are much more expensive than amoxicillin. Clindamycin and azithromycin are effective in 90% and 80% of cases, respectively.

• Inpatient treatment: For pts with noncritical illness, β-lactam antibiotics are recommended—e.g., penicillin (3–4 mU IV q4h) or ceftriaxone (1 g IV q12–24h). For pts with critical illness, vancomycin may be added, with its use reviewed once susceptibility data are available.

• Treatment duration: The optimal duration of treatment is uncertain, but continuation of antibiotics for at least 5 days after the pt becomes afebrile seems prudent.

• Because of the increased prevalence of resistant pneumococci, first-line therapy should include vancomycin (1 g IV q12h) plus a third-generation cephalosporin (ceftriaxone, 2 g IV q12h; or cefotaxime, 2 g IV q4h). Rifampin (600 mg/d) can be substituted for the third-generation cephalosporin in pts hypersensitive to β-lactam agents.

• The antibiotic regimen should be adjusted appropriately once susceptibility data are available. If the isolate is resistant to penicillin and cephalosporins, both vancomycin and the cephalosporin should be continued.

• A repeat LP should be considered after 48 h if the organism is not sensitive to penicillin and information on cephalosporin sensitivity is not yet available, if the pt’s clinical condition does not improve or deteriorates, or if the pt has received dexamethasone, which may compromise clinical evaluation.

• In adults with community-acquired bacterial meningitis, dexamethasone should be given before or in conjunction with the first dose of antibiotics, as glucocorticoids have been demonstrated to significantly reduce rates of mortality, severe hearing loss, and neurologic sequelae. The data are not clear as to whether this practice is also beneficial in children.

• All persons ≥65 years old and those 2–64 years old who are at increased risk of pneumococcal disease should receive the 23-valent pneumococcal polysaccharide vaccine (PPSV23), which contains capsular polysaccharide from the 23 most prevalent serotypes of S. pneumoniae.

  • – Persons >2 years old with continuing increased risk should be revaccinated every 5 years.

  • – Persons whose only indication for vaccination is an age of ≥65 years do not need to be revaccinated.

• The efficacy of PPSV23 is controversial; it appears to be effective against invasive pneumococcal disease but less effective or ineffective against nonbacteremic pneumococcal pneumonia.

• The duration of protection conferred by PPSV23 is ~5 years.

• The poor response of infants and young children to pneumococcal polysaccharide vaccines prompted the development of pneumococcal conjugate vaccines. In the United States, the current recommendation is for infants to be routinely vaccinated with the conjugate vaccine PCV13, which contains the 13 serotypes most associated with disease.

  • – All immunocompromised children and adults should receive PCV13 prior to receiving PPSV23.

  • – Pneumococcal conjugate vaccines are highly effective at providing protection against vaccine-serotype invasive pneumococcal disease, pneumonia, otitis media, nasopharyngeal colonization, and all-cause mortality.

  • – In the United States, there has been a >90% reduction in vaccine-serotype invasive pneumococcal disease among the whole population, including indirect protection of unvaccinated adults.